MLL-ENL Inhibits Polycomb Repressive Complex 1 to Achieve Efficient Transformation of Hematopoietic Cells

Mäthner E, Garcia-Cuellar MP, Breitinger C, Takacova S, Divoky V, Hess JL, Slany R (2013)

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2013

Journal

Book Volume: 3

Pages Range: 1553-1566

Journal Issue: 5

DOI: 10.1016/j.celrep.2013.03.038

Abstract

Stimulation of transcriptional elongation is a key activity of leukemogenic MLL fusion proteins. Here, we provide evidence that MLL-ENL also inhibits Polycomb-mediated silencing as a prerequisite for efficient transformation. Biochemical studies identified ENL as a scaffold that contacted the elongation machinery as well as the Polycomb repressive complex 1 (PRC1) component CBX8. These interactions were mutually exclusive invitro, corresponding to an antagonistic behavior of MLL-ENL and CBX8 invivo. CBX8 inhibited elongation in a specific reporter assay, and this effect was neutralized by direct association with ENL. Correspondingly, CBX8-binding-defective MLL-ENL could not fully activate gene loci necessary for transformation. Finally, we demonstrate dimerization of MLL-ENL as a neomorphic activity that may augment Polycomb inhibition and transformation. © 2013 The Authors.

Authors with CRIS profile

Involved external institutions

Palacky University Olomouc / Univerzita Palackého v Olomouci Czech Republic (CZ) University of Michigan United States (USA) (US)

How to cite

APA:

Mäthner, E., Garcia-Cuellar, M.-P., Breitinger, C., Takacova, S., Divoky, V., Hess, J.L., & Slany, R. (2013). MLL-ENL Inhibits Polycomb Repressive Complex 1 to Achieve Efficient Transformation of Hematopoietic Cells. Cell Reports, 3(5), 1553-1566. https://doi.org/10.1016/j.celrep.2013.03.038

MLA:

Mäthner, Emanuel, et al. "MLL-ENL Inhibits Polycomb Repressive Complex 1 to Achieve Efficient Transformation of Hematopoietic Cells." Cell Reports 3.5 (2013): 1553-1566.

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